This proposed project will investigate and characterize the capabilities of platinum anti-cancer drugs (platinum coordination complexes) to potentiate the therapeutic effects of ionizing radiation on mammalian cells and animal tumors. The parent compound in this family of new drugs, cis-dichloro-diammineplatinum(II), is known to be a potent radiosensitizer of hypoxic bateria. Preliminary results obtained in our laboratory indicate that it should be possible to extend this synergism between the two modalities to tumor cells, confirming a suggestion presented originally by Richmond and Powers. One objective of this proposed study is to examine the action of a variety of platinum compounds on mammalian cells in culture when used alone or in combination with ionizing radiation. Two cell lines will be used, a mouse mammary adenocarcinoma, MTG-B, and a Chinese hamster lung fibroblast V-79. The cells will be treated under various growth conditions, including log phase and plateau phase, and the V-79 cells will also be treated as three-dimensional spheroids. The cells will be treated in the presence and absence of oxygen using a special gassing apparatus for the production of chronically hypoxic cells. A second objective is to test for the radiosensitization of hypoxic tumor cells treated in situ. Survival of the transplantable MTG-B cells will be assayed following combined therapy using the tumor latency assay in C mice. The combined therapy will be studied using a rat brain tumor (gliosarcoma). The brain tumor cells will be implanted intracerebrally and the growth and host lifespan will be examined following treatment of advanced solid tumors. Results of these studies should identify radiosensitizers and treatment conditions that could improve clinical tumor response.